1. Field of the Invention
The invention is generally in the field of cationic steroidal anti-microbial compounds that mimic anti-microbial peptides and methods for making particulates of these compounds.
2. Related Technology
Ceragenin compounds, also referred to herein as cationic steroidal anti-microbial compounds (CSAs), are synthetically produced small molecule chemical compounds that include a sterol backbone having various charged groups (e.g., amine and cationic groups) attached to the backbone. Ceragenins are thought to mimic the structure and function of naturally-occurring anti-microbial peptides and are able to kill and/or sensitize bacteria, fungi, and other microbes.
Ceragenins are able to kill bacteria, fungi, lipid-enveloped viruses, and other microbes by associating with the outer membrane of the microbe and then inserting into the membrane. When inserted into the membrane, ceragenins disrupt the cell's outer membrane and increase ion permeability. Most microbes cannot survive if their membranes are “permeablized” because they, for example, depend on transmembrane ion gradients for ATP production and maintenance of other vital cell functions.
Ceragenins are readily soluble in water and, like most antibiotics, their effectiveness can be diminished or eliminated if they are washed away or diluted. As a result, ceragenins and other antibiotics are generally not very effective for inhibiting microbial growth on surfaces. One technique that has been explored for making antibiotics more active on surfaces (e.g., polymer surfaces) is to covalently attach the antibiotic to the surface. For example, U.S. Pat. No. 7,854,941 to Urban et al. describes a system for covalently attaching antibiotics (e.g., β-lactam antibiotics) to reactive moieties that are themselves covalently attached to a polymer surface. By selecting appropriate antibiotics, growth of both Gram-negative and Gram-positive bacteria on the polymer surface can be inhibited by such a system.
Alternatively, anti-microbial compounds are delivered in a fluid medium and periodically reapplied to a surface to maintain a low microbial count.